The underlying causes of aging and longevity are largely unknown and currently are a topic of fervent debate. Most traditional model species in aging research are chosen partially because they are unable to combat the aging process and have short life-spans. An alternative approach is the study of species with prolonged longevity, for these animals may exhibit retarded senescence, possess superior anti-aging defenses and thus may explicate the aging process. One such animal is the naked mole-rat, Heterocephalus glaber. These mouse-sized (about 40g) rodents have a maximum life-span of more than 27 years and live eight times longer than predicted by body mass. They continue to breed at these ages and also age-related declines in physiological function are attenuated. The proposed pilot study aims to characterize the aging process in naked mole-rats in an integrative manner incorporating in vivo organismic function in addition to in vitro biochemical studies. Specific questions I will address include a) what is the effect of aging on resting, maximal and daily energy expenditure? b) can the differential longevity of mice and mole-rats be attributed to unequal generation of reactive oxygen species (ROS) and/or disparate antioxidant activities? and c) is there a difference in agerelated advanced glycation end products (AGEs) in mice and naked mole-rats? Preliminary data reveal that neither resting nor peak metabolic rates are attenuated with age. These data suggest that the lifetime energy expenditure of naked mole-rats is indeed exceptional such that they must be potentially exposed to considerable oxidative damage and glycemic stress. Oxidative damage, anti-oxidant defense and AGEs will be assessed in tissues harvested from naked mole-rats and shorter-lived mice at both equivalent life-stages (young, middle-aged and old) and at equal levels of lifetime energy expenditure. While anti-oxidant defense, (as indicated by superoxide dismutase activity) of naked mole-rats is superior to that of mice, the different levels of anti-oxidant activity do not appear to be sufficient to account for the extraordinary longevity. Other mechanisms must also contribute to the retarded aging process. In this study, I propose that the naked mole-rat is an excellent new animal model for mammalian aging research. Its astonishing longevity coupled with our preliminary data suggest aging processes in this rodent are indeed retarded. In depth understanding of aging in naked mole-rats thus warrants further research and has the potential to contribution substantially to our understanding of the mechanisms involved in this fundamental processes.